The present invention pertains generally to substitute heart valves, and more particularly to tissue-engineered cardiovascular valves.
The introduction of substitute heart valves (SHV""s) into clinical practice in the 1960""s resulted in a dramatic improvement in the longevity and symptomatology of patients with valvular heart disease. However, major problems remain. With the exception of autograft and allograft aortic valves and repaired mitral valves, the 10-year mortality after valve replacement with either mechanical or bioprosthetic valve ranges between 30 and 55 percent. The incidence of thromboembolic complications is 1.5-3.0 per 100 patient-years (percent/year); prosthetic valve endocarditis averages approximately 0.5 percent/year. The incidence of bleeding complications is 1.5-3.0 percent/year for anticoagulated patients and approximately one-third that rate for patients who are not anticoagulated. The reoperation rate ranges between 2 and 4 percent/year; by 10 years one-third of bioprosthetic valves require replacement and by 15 years more than two-thirds do. Autografts and allograft aortic valve substitutes have limited availability and require longer and more complicated surgery; therefore, these valve substitutes are prescribed for younger patients, generally below age 60. Mitral valve repair is helpful in approximately two-thirds of patients, but often is less suitable for older patients and decreases but does not eliminate the morbidity of bioprosthetic valves. These data loudly announce and convincingly certify that SHV""s developed and approved for clinical use 15-30 years ago replace one disease with another and are far from ideal.
Better SHV""s that can be quickly and safely implanted in older patients who often have comorbid disease are needed. Incremental improvements in existing mechanical and bioprosthetic heart valves may help, but visionary new designs and new approaches that specifically address the complications of reduced lifespan, thromboembolism, the need for anticoagulation, endocarditis and structural deterioration are more appropriate goals for our biotechnical effort. New biomaterials and surface coatings, new mechanical valve designs, longer lasting hemodynamically normal xenografts and tissue-engineered valves from autologous cells are some of the new ideas for developing an ideal heart valve substitute.
Development of truly new SHV""s requires a multidisciplinary approach, spanning clinical science, cell and molecular biology, materials science and bioengineering. Although much is known regarding the mechanisms of thromboembolism, endocarditis, structural deterioration and other morbid events, much more basic information is needed before a SHV becomes a xe2x80x9ccure.xe2x80x9d
Thus, while mechanical and bioprosthetic heart valves (mhv and bhv) have made a dramatic impact since their introduction in the 1960""s, the 10-year mortality after replacement is relatively high, with undesirable reoperation rates because of mechanical failure (mhv), bleeding and thromboembolic complications (mhv and bhv), and calcification (bhv). Autografts and allografts, while more successful, fall far short in supply. The need is particularly great for juveniles since neither mhv nor bhv have the capacity to grow. Thus, there is great interest in developing a new generation of substitute heart valves based on tissue-engineering approaches (1).
We have developed a mold to fabricate multileaflet xe2x80x9cvalve-equivalentsxe2x80x9d based on the tissue-equivalent approach of entrapping tissue cells in a self-assembled biopolymer scaffold. The mold design results in leaflet structures possessing circumferential alignment of protein fibers characteristic of native leaflets. Accordingly, the present invention provides method and apparatus for forming one or more substitute valve leaflets from a solution of fibrillar biopolymer gel and tissue cells, wherein there is provided a female surface and a male surface adapted to cooperate with the female surface to define a compaction volume therebetween for receiving the solution, wherein the method and apparatus is adapted to produce one or more contiguous substitute valve leaflets having structural alignment and mechanical properties which mimic those of natural valve leaflets.